Structural modifications of CH(OH)-DAPYs as new HIV-1 non-nucleoside reverse transcriptase inhibitors.

Authors :: Yan ZH
Huang XY
Wu HQ
Chen WX
He QQ
Chen FE
De Clercq E
Pannecouque C
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2014 Apr 15; Vol. 22 (8), pp. 2535-41. Date of Electronic Publication: 2014 Mar 04.
Publication Year :: 2014
Abstract: A series of CR2(OH)-diarylpyrimidine derivatives (CR2(OH)-DAPYs) featuring a hydrophobic group at CH(OH) linker between wing I and the central pyrimidine were synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. All the target compounds except for compound 3k displayed inhibitory activity against HIV-1 wild-type with EC50 values ranging from 7.21±1.99 to 0.067±0.006 μM. Among them, compound 3d showed the most potent anti-HIV-1 activity (EC50=0.067±0.006 μM, SI>592), which was approximately 2-fold more potent than the reference drugs nevirapine (NVP) and delaviridine (DLV) in the same assay. In addition, the binding modes with HIV-1 RT and the preliminary SAR studies of these new derivatives were also investigated.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Subjects :: Binding Sites
Cell Line
HIV Reverse Transcriptase metabolism
Humans
Molecular Docking Simulation
Protein Structure, Tertiary
Pyrimidines chemistry
Pyrimidines metabolism
Reverse Transcriptase Inhibitors metabolism
Structure-Activity Relationship
HIV Reverse Transcriptase antagonists & inhibitors
HIV-1 enzymology
Reverse Transcriptase Inhibitors chemistry

Full Text Access

Tools